Human DICER helicase domain recruits PKR and modulates its antiviral activity.


Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
05 2021
Historique:
received: 02 12 2020
accepted: 08 04 2021
entrez: 13 5 2021
pubmed: 14 5 2021
medline: 5 10 2021
Statut: epublish

Résumé

The antiviral innate immune response mainly involves type I interferon (IFN) in mammalian cells. The contribution of the RNA silencing machinery remains to be established, but several recent studies indicate that the ribonuclease DICER can generate viral siRNAs in specific conditions. It has also been proposed that type I IFN and RNA silencing could be mutually exclusive antiviral responses. In order to decipher the implication of DICER during infection of human cells with alphaviruses such as the Sindbis virus and Semliki forest virus, we determined its interactome by proteomics analysis. We show that DICER specifically interacts with several double-stranded RNA binding proteins and RNA helicases during viral infection. In particular, proteins such as DHX9, ADAR-1 and the protein kinase RNA-activated (PKR) are enriched with DICER in virus-infected cells. We demonstrate that the helicase domain of DICER is essential for this interaction and that its deletion confers antiviral properties to this protein in an RNAi-independent, PKR-dependent, manner.

Identifiants

pubmed: 33984068
doi: 10.1371/journal.ppat.1009549
pii: PPATHOGENS-D-20-02587
pmc: PMC8118307
doi:

Substances chimiques

Antiviral Agents 0
Interferon Type I 0
EIF2AK2 protein, human EC 2.7.11.1
eIF-2 Kinase EC 2.7.11.1
DICER1 protein, human EC 3.1.26.3
Ribonuclease III EC 3.1.26.3
DEAD-box RNA Helicases EC 3.6.4.13

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1009549

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Thomas C Montavon (TC)

Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, Strasbourg, France.

Morgane Baldaccini (M)

Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, Strasbourg, France.

Mathieu Lefèvre (M)

Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, Strasbourg, France.

Erika Girardi (E)

Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, Strasbourg, France.

Béatrice Chane-Woon-Ming (B)

Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, Strasbourg, France.

Mélanie Messmer (M)

Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, Strasbourg, France.

Philippe Hammann (P)

Université de Strasbourg, CNRS, Institut de Biologie Moléculaire et Cellulaire, Plateforme Protéomique Strasbourg-Esplanade, Strasbourg, France.

Johana Chicher (J)

Université de Strasbourg, CNRS, Institut de Biologie Moléculaire et Cellulaire, Plateforme Protéomique Strasbourg-Esplanade, Strasbourg, France.

Sébastien Pfeffer (S)

Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, Strasbourg, France.

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